Two concurrent studies assessing the value of adjuvant chemotherapy and adjuvant chemoimmunotherapy in head and neck cancer patients with a high risk of recurrent disease are proposed. Patients from one treatment center will be stratified and randomized to receive or not chemotherapy (methotrexate plus leucovorin) in addition to standard therapy (surgery and/or radiation therapy). Patients at a second center will be similarly stratified and randomized to receive chemotherapy or chemoimmunotherapy with autochthonous, neuraminidase treated tumor cell vaccine plus BCG. All patients will be followed for disease-free and actuarial survival. We will follow the frequency of occurrence of a second primary malignancy to assess the role of immunotherapy in immunoprophylaxis in this patient population at high risk of such development. In addition all patients will be immunologically monitored with skin tests to common recall antigens, IgM, IgG and IgA immunoglobulin quantitation, T-cell quantitation assessing "active" and "total" populations, and mitogen blastogenic stimulation to PHA, LPS and PPD. All tests will be monitored every 3 months and in vitro lymphocyte studies will be repeated twice weekly during therapy. Results will be recorded and stored on CDC model 6400 computer and retrieved for multivariate analysis of variance to examine interrelationships of data. In addition techniques for specific tumor immune responsiveness assessing lymphocyte blast genesis to neuraminidase-treated tumor cells vs. normal autochthonous tissue will be investigated. Concurrent control and specific immunotherapy treated populations are ideal for assessing the value of such specific immunologic monitoring techniques. These studies are based on encouraging 2 year disease free survival using this schedule of methotrexate and leucovorin prior to surgery and radiation therapy and on peliminary data suggesting adjuvant immunotherapy may increase the effect. The current proposal is required to establish the efficacy of this therapy.